CN102088959B - Tablet matrix that can directly compress and quickly disintegrated - Google Patents

Tablet matrix that can directly compress and quickly disintegrated Download PDF

Info

Publication number
CN102088959B
CN102088959B CN200980127245.8A CN200980127245A CN102088959B CN 102088959 B CN102088959 B CN 102088959B CN 200980127245 A CN200980127245 A CN 200980127245A CN 102088959 B CN102088959 B CN 102088959B
Authority
CN
China
Prior art keywords
blend
tablet
purposes
carrier material
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN200980127245.8A
Other languages
Chinese (zh)
Other versions
CN102088959A (en
Inventor
D·克雷恩沃驰尔
G·莫德尔莫格
R·欧吉尼比尼
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41134695&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN102088959(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of CN102088959A publication Critical patent/CN102088959A/en
Application granted granted Critical
Publication of CN102088959B publication Critical patent/CN102088959B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Nutrition Science (AREA)
  • Oncology (AREA)
  • Immunology (AREA)
  • Hospice & Palliative Care (AREA)
  • Otolaryngology (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pulmonology (AREA)
  • Biochemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to the matrix that can directly compress, this matrix is for the preparation of under wet environment, especially in oral cavity, and quickly disintegrated tablet.

Description

Tablet matrix that can directly compress and quickly disintegrated
The present invention relates to the matrix that can directly compress, this matrix is for the preparation of quickly disintegrated tablet under existing at moisture.
Technical field
For from Peroral solid dosage form pharmaceutical formulation, particularly release of active ingredients fast from tablet, needs tablet matrix very quickly disintegrated, that mouthfeel is joyful and that be easy to processing. This base material must be provided and be had tablet less abrasion and that hardness is enough by compression simultaneously, so as after its preparation for further processing as for packaging, and make the patient can excellent operation.
Sweet mellow wine provides the foundation for this type of matrix, because after suitable pretreatment, it has well compressible, good bin stability, is compatible with nearly all active component, tastes simultaneously and has pleasant sweet taste.
But the mannitol formulations for this application target existing in the market or prepare very complicated structure, and/or is to be inadequate on its pharmaceutical properties.
Ask a question
Unified in this type of suitable preparation to two of this type of tablet matrix contrary requirements (thering is high tablet hardness in very quick disintegration release of active ingredients). In addition, this matrix should can be highly susceptible to processing in industrialization tablet manufacturing, and itself and other tablet ingredients can directly be compressed without granulation step.
Deal with problems
Find by test at present, by the blend of specific sweet mellow wine powder and crosslinked sodium carboxymethylcellulose is provided, in direct tablet compressing technique, obtain the tablet matrix for the preparation of the special granular texture of having of rapid disintegration tablet and large BET surface area.
Therefore theme of the present invention is the blend for the preparation of rapid disintegration tablet in direct tablet compressing technique, this blend is by 90-98 weight portion, the particularly preferably spray-dired sweet mellow wine of 95 weight portions and 10-2 weight portion, the particularly preferably crosslinked sodium carboxymethylcellulose composition of 5 weight portions, it is characterized in that thering is the 1.5m of being greater than2The BET surface area of/g. Be proved to be especially particularly advantageously, in the time using mixture, its BET surface area is at 1.9-4.0m2In the scope of/g, particularly at 1.9-2.6m2Within the scope of/g. Be proved to be completely particularly advantageously, in the time using corresponding mixture for the preparation of tablet, have bulk density is that 0.45-0.60g/ml, compacted density are that 0.60-0.75g/ml and mobile inclination angle are 30-38 ° simultaneously.
In this type of blend of the present invention, particle has average grain diameter (laser determination) in the scope of 60-200 μ m, preferably in the scope of 64-114 μ m. Mixture to be used preferably has the water content of < 1 % by weight.
The blend with these character can be pressed into tablet in simple mode. After the pressure lower compression of 20kN, can obtain the tablet with hardness > 250N, it has friability≤0.14% and disintegration time≤70 second.
Particularly, blend according to the present invention be suitable for use as carrier material for have described favourable character containing active component and/or containing the tablet formulation agent of spices, and the tablet or do not have with active component or the other medicines preparaton prepared by this carrier material.
The character favourable according to it, support according to the present invention material is particularly useful for making the tablet formulation agent that contains active component and spices. Described active component and spices can be particularly:
The material of-nutrition supplement class, as vitamin, mineral matter, trace element, functional food component, as plant component and plant extracts.
-lower class material: synthetic and natural dyestuff; Natural with give the material of taste with natural consistent spices and other, as sweetener (Aspartame, asccharin, acesulfam-K K, neohesperidin DC, sucralose; Thaumatin T (Thaumatin) and stevioside), fruit flavors, mint flavouring or menthol; Tartaric acid, as citric acid and tartaric acid; Give the plant extracts of taste etc.
-there is the material of pharmacotoxicological effect, as antiacid, anti-infective, it is also in oral cavity and throat's local action;
-comprise the anodyne of opioid, antiallergic, antiemetic, antidiarrheal agent, etc.
Detailed Description Of The Invention
By by spray-dired sweet mellow wine (ParteckM, MerckKGaA) with so-called super-disintegrant, for example crosslinked Na-CMC (Ac-Di-Sol, FMCBioPolymer) combination (mixing) can obtain the tablet matrix that can directly compress, and it shows (niedrige) disintegration character of constant short time under the hardness range of non-constant width. For example, with sweet mellow wine-super-disintegrant-composition (Ludiflash; BASF) CO-spray-drying thing or by compared with the situation that obtainable other business directly sweet mellow wine of compression-type (DC-Mannit) is mixed with crosslinked Na-CMC, this very short disintegration time is kept under obviously wider hardness range. In addition, surprisingly, by this mixed process, although there is huge mechanical load, do not damage the direct tablet compressing character (DC character) of sweet mellow wine.
Therefore, continue to add worker use obtained material by simply mix with its formula components and with simple mode subsequently direct tablet compressing can obtain very quickly disintegrated tablet, as ODT (the dispersible tablet in oral cavity). This very quick disintegration is the basic premise that quick active component discharges, relevant to the quick absorption of APIs, for example, in oral cavity and throat.
Mixing (as in screw rod cone blender) be made up of with 10-2 weight portion super-disintegrant 90-98 weight portion ParteckM (preferably ParteckM200), preferably meets with flying colors these requirements with crosslinked Na-CMC as the composition that Ac-Di-Sol forms. In view of hardness/disintegration time ratio, use by 95% ParteckM200 and 5% Ac-Di-SolTypSD-711; The mixture of FMCBioPolymer composition obtains best result.
Preparation the present invention can with Powdered sweet mellow wine can carry out according to the disclosed method of patent documentation EP0896528B1. Preferably be prepared by corresponding spray drying process. But it also can be undertaken by fluidized bed prilling. The method is carried out as follows:
A) prepare moisture mannitol solution, it can optionally contain on a small quantity other polyalcohol of (in the total amount of sweet mellow wine and other polyalcohol, the optional amount with the highest 2 % by weight), and
B1) gas flow temperature for 120-300 DEG C at the dry solution obtaining of spraying, wherein, the water in evaporating liquid, or
B2) stir the solution that obtains in gas flow temperature at for 40-150 DEG C, wherein, the water in evaporating liquid.
By means of nozzle, preferably by means of centrifugal atomizer, be warmed up to 120-300 DEG C, preferably, in the temperature of 140-190 DEG C, dry, the centrifugal air-flow blasting, spray by spraying. The amount of the polyhydric alcohol solutions adding and the hot gas blasting is so coordinated with each other, makes polyalcohol dry until water content is about 0.3-approximately 1 % by weight. In all cases, water content should be below 1 % by weight.
The polyalcohol condensation product obtaining by the dehydration of polyalcohol droplet is raised to the temperature of approximately 70 DEG C of about 50-under spraying is dry, and the air blasting is during this period cooled to approximately identical temperature. The sweet mellow wine quality so makingBe collected in container, and be suitable for directly preparing tablet or compacting product after cooling.
But also possibly, carry out the preparation of the spendable sweet mellow wine of the present invention thering is the mode that in a continuous manner, optionally adopts powder to feed back for the equipment of the fluid bed of rear dry spray-dried materials. Corresponding equipment is well known by persons skilled in the art, as by patent documentation EP1453781B1 and EP1319644B1 or by WO00/76650A1. This kind equipment allows those skilled in the art to regulate the extra spraying of powder bed, air-flow, temperature control (Temperaturf ü hrung) and optional extra initial soln by specific aim, and the controlled product of fine materials feeds back again, regulate the particle diameter of desired particle. Simpler equipment is in patent documentation EP0738252B1 or EP0904059B1.
The sweet mellow wine so obtaining also has large surface area except thread micro-structural. Desired Size particles contained in prepared powder can regulate targetedly by the operational factor of selecting spray drying device or fluidized bed prilling equipment. But also possible that, be divided into the upper particle of sieve and the lower particle of sieve by sieve, and regulate thus the particle diameter of sweet mellow wine powder in the scope of 60-200 μ m, preferably in the scope of 64-114 μ m. The correlation method sieving under temperate condition is known to those skilled in the art. Commercially corresponding product can, at trade mark ParteckM by name, obtain as under ParteckM200.
As above as described in, find by test, the carrier material that the blend being made up of with specific mixing ratio based on weight sweet mellow wine and the so-called super-disintegrant of above-mentioned quality can be prepared for the preparation of tablet, it provides the tablet with relatively high tablet hardness under the compression of relatively little pressure, but disintegration under relatively short time inherent moisture environment.
In this article, commercially available crosslinked Na-CMC is proved to be suitable super-disintegrant, and it can commercially obtain at extensive stock under one's name, and has at the same time and under enough large surface areas, have equally less average grain diameter. Preferably use average grain diameter within the scope of 10-100 μ m, the preferably crosslinked Na-CMC within the scope of 20-50 μ m.
Find by contrast test, according to product of the present invention, by 90-98 part ParteckM and 10 to 2 parts of super-disintegrant, preferably with crosslinked Na-CMC, as the mixture of Ac-Di-Sol composition, and do not add crosslinked Na-CMC as compared with the known spraying drying type sweet mellow wine of carrier material, particularly under higher pressure limit, show the tablet hardness of improving, that is, they especially do not demonstrate " becoming cap (Deckeln) " tendency. In addition, according to the present invention, the disintegration time of product is significantly less than and does not add the tablet obtaining under the spraying drying type sweet mellow wine of crosslinked Na-CMC as carrier material using.
Compared with product of the present invention, although the CO-spray-drying product that contains 95 portions of sweet mellow wine and 5 parts of crosslinked Na-CMC has similar tablet hardness (with showing also there is no " becoming cap tendency "), have obviously longer at thisDisintegration time. These contrast materials are prepared according to described method, and difference is to treat that Na-CMC crosslinked described in spray-dired mannitol solution is corresponding to sweet mellow wine and crosslinked Na-CMC95: 5 ratio (as dry) and continuing to stir under be dried by spraying under the described conditions or fluidized bed prilling by CO-spray-drying together with them.
Also find, compared with the tablet being obtained by conventional commercially available prod, the disintegration time of the tablet that blend forms according to the present invention is shorter exceeding under wider hardness range. Thus, material according to the invention is applicable to compounding pharmaceutical composition in direct tablet compressing technique especially well, is also applicable to especially the tablet of preparation quick release of active ingredients in oral cavity.
Further, with obtainable by business, for compared with the prepared tablet of the CO-spray-drying thing (Ludiflash) of the sweet mellow wine/Crospovidone/polyvinyl acetate/PVP of ODT preparaton, obtain within the scope of larger tablet hardness quickly disintegrated tablet in proportion by using according to blend according to the present invention. In addition can, as already mentioned, using under similar pressure, use according to mixture of the present invention and realize higher tablet hardness. This is particularly advantageous for the active component of the difficult compression of preparation for pharmacists, and allows pharmacists more easily to carry out compressing tablet.
But compared with blend according to the present invention, even if the Pearlitol200SD that is equally a kind of spray-dired sweet mellow wine demonstrates poor compressing tablet behavior after mixing with AcDiSol, same is other compressible type sweet mellow wine based on crystallization or particle, they show as worse cementing property, particularly high friability.
Implement, be illustrated in Fig. 1 according to the result of compressing tablet of the present invention test and comparative example, wherein record the disintegration time of prepared tablet for obtained tablet hardness.
Compared with commercial known carrier material by document with using those skilled in the art, in an advantageous manner, in the time using blend according to the present invention to prepare for tablet as matrix, under similar pressure, can obtain harder tablet.
Find further, when in order to treat as well as possible compressing tablet instrument and compressing tablet machine when preferably to the low-pressure scope lower sheeting of 20kN, by using material according to the invention to obtain very good cementing property. In addition, the tablet obtaining shows very good mechanical stability, and the obvious < 1% of friability of detection, guarantees the safety operation of press body thus.
The present invention describes and makes those skilled in the art can comprehensively apply the present invention. Therefore even without other embodiment, those skilled in the art can set out thus above-mentioned explanation is used in the widest scope.
Why not clearly, in situation in office, self-evidently should adopt quoted publication and patent documentation. Therefore these documents are considered to be a part for the disclosure of the present invention's description.
In order better to understand and to illustrate the present invention, provide in following two embodiment, it is within protection scope of the present invention. These embodiment are also for explaining possible version. But according to the universal validity of described invention principle, these embodiment are unsuitable for the application's protection domain only for thereon.
In addition, to those skilled in the art self-evidently, in the other parts of the embodiment providing and description, based on whole composition, in composition the amount of contained component in total amount always add up to be only 100 % by weight or % by mole, and can not exceed, even obtain higher value by given percentage range. As without other explanation, % data be therefore regarded as % by weight or % by mole, outside the ratio representing divided by volume data.
The temperature providing in embodiment and description and in claims adopts DEG C always.
Embodiment
For exosyndrome material, use following analytical method:
-bulk density: according to DINENISO60
-compacted density: according to DINENISO787-11:1995
-angle of rest (repose): according to DINISO4324
What-particle diameter distributed determines: adopt the dry dispersion of Mastersizer2000 version 5.10G laser light scattering, the 34403-97 of series number: MalvernInstrumentsLtd; Dispersal unit Scirocco2000 (A), counter-pressure 1 bar; Evaluation model: Universal; Fraunhofer; Carry out according to technical manual and manufacturers instruction.
The test of-tableted:
By the material of its tableted character to be tested 495g and 5gParteckLUBMST (plant-derived dolomol) EMPROVEexpPhEur, BP, JP, NF, FCCArt.Nr.1.00663 (MERCKKGaA, Germany) blending, this dolomol is in advance through 250 μ m sieve screenings, and at the rustless steel container [container volume: approximately 2 liters of sealing, highly: about 19.5cm, diameter: about 12cm, external dimensions] in mix 5 minutes in the laboratory Taumel-blender [Turbula, Fa.WillyA.Bachofen (Schweiz)].
At the upper tablet (11mm die, circle, put down, have facet) that is pressed into 500mg with the evaluation system Catman5.0 of HottingerBaldwinMesstechnik-HBM (Germany) company of unfaithful intention-tablet press machine KorschEK0-DMS of instrumentation (Fa.KORSCH1 Germany).
Depending on used pressure (5,10,20 and 30kN; Each +/-10%) and determine, prepare at least 100 tablets for evaluating the condition code (Kennzahlen) of pharmacy.
The mensuration of-tablet hardness, diameter and height: ErwekaTBH30MD; Fa.Erweka (Germany); Obtain average datas by 20 tablets of each mensuration under each pressure
-tablet abrasion: the friability detector of Fa.Erweka (Germany); The enforcement of instrument parameter and detection is according to " the friability of non-coated tablet of the 5th edition PhEurvonnichtüberzogenenTabletten)”
-tablet quality: 20 tablets obtain average by weighing; The MettlerAT201 of scale: Fa.Mettler (Germany)
The automatic tablet tester disi4 of-disintegration of tablet: Fa.Biomation (Germany); Medium: the water of desalination at 37 DEG C; The enforcement of instrument parameter and detection is according to the 5th edition PhEur " friability of non-coated tablet "
-BET surface area: evaluate and implement according to document " BETSurfaceAreabyNitrogenAbsorption " people such as S.Brunauer (JournalofAmericanChemicalSociety, 60,9,1938) and DINISO9277; The ASAP2420 of instrument: MicromeriticsInstrumentCorporation (USA) company; Volume method; Nitrogen; With sample preparation about 3g+/-5% (heat 3.0 DEG C/min until target temperature 50 DEG C) of weighing: 10 hours/50 DEG C
Operation, storage, reprocessing and the test of particle and compression body at the temperature of 19-25 DEG C and relative humidity in the scope of 20-35%, carry out.
Characterize: blend (95: the 5) (AcDiSolTypSD-711 of the crosslinked Na-CMC of 95 granular weight portion sweet mellow wine and 5 weight portions; FMCBioPolymer) (2 embodiment)
Compressing tablet data: the blend (2 embodiment) of the granular mannitol of 95: 5 and crosslinked Na-CMC with do not add crosslinked Na-CMC granular mannitol contrast and with the contrast (each ratio is in weight portion) of the CO-spray-drying thing of the Na-CMC of the sweet mellow wine of 95: 5/crosslinked
Compared with not adding the spraying drying type sweet mellow wine of crosslinked Na-CMC, show the tablet hardness of improving especially in higher pressure limit according to product of the present invention, especially there is no " becoming cap tendency ". In addition, according to the present invention, the disintegration time of product is obviously faster.
Compared with product according to the present invention, although the CO-spray-drying product that contains the 95 weight portion sweet mellow wine Na-CMC crosslinked with 5 weight provides similar tablet hardness (and also showing there is no " becoming cap tendency "), disintegration time obviously extends.
Compressing tablet data: according to product of the present invention (2 embodiment) and 95: 5 (weight portion) by the direct commercially available sweet mellow wine (Pearlitol200SD of compression-type, Pearlitol300, Mannogem2080, Mannogem3215) and the contrast of the blend of crosslinked Na-CMC (AcDiSolTypSD-711) composition and with the contrast of the CO-spray-drying thing being formed by sweet mellow wine/Crospovidone/polyvinyl acetate/PVP (Ludiflash) directly compressible, that evaluate for ODT preparaton
Compared with the sweet mellow wine/Crospovidone/polyvinyl acetate/PVP (Ludiflash) of the CO-spray-drying obtaining for ODT preparaton, exceeding under higher tablet hardness scope with product according to the present invention, can obtain quickly disintegrated tablet in proportion. In addition, under similar pressure, use according to product of the present invention and can realize higher tablet hardness, this means and frees in the time that preparation is difficult to the active component of compression for pharmacists.
Pearlitol200SD, be a kind of spray-dired sweet mellow wine equally, compare with product according to the present invention and demonstrate equally the poor compressing tablet behavior the same with other directly compressibility sweet mellow wine (it is also taking worse cementing property (particularly high friability) as feature) taking crystallization or particle as basis.
The result of above-described embodiment and comparative example is illustrated in Fig. 1, wherein records the disintegration time of prepared tablet for obtained tablet hardness, with Ludiflash, and the Pearlitol200SD of BASF and 95: 5; Roquette and crosslinked Na-CMC (Ac-Di-SolTypSD-711, FMCBioPolymers) mixture is compared, and Fig. 1 shows the correlation in lower disintegration of tablet time of 4 pressure (5,10,20 and 30kN) and obtainable tablet hardness according to product of the present invention (2 embodiment). Contrary with two comparative examples, product of the present invention is also also presented under obviously higher tablet hardness still disintegration time rapidly.
In a word, compared with prior art, under similar pressure, use according to product of the present invention and can obtain harder tablet.
In the preferred pressure limit in order to treat as well as possible compressing tablet instrument and compressing tablet machine, this material has shown very good cementing property thus. The obvious < 1%-of friability of this very good mechanical stability-detection guarantees the safety operation of press body.
Meanwhile, compared with the tablet being obtained by conventional commercially available prod, disintegration time is short under the hardness range of non-constant width. Thus, material according to the invention is applicable to compounding pharmaceutical composition in direct tablet compressing technique especially well, is also applicable to especially the tablet of preparation quick release of active ingredients in oral cavity.
BET surface area: be according to the summary of the surface area of the composition contrasting of BET method detection below. As above as described in, as at " BETSurfaceAreabyNitrogenAbsorption ", the people such as S.Brunauer (JournalofAmericanChemicalSociety, 60,9,1938) such these values of measuring or described in DINISO9277. In order to measure, use the instrument of MicromeriticsInstrumentCorporation (USA) [ASAP2420] company. This detection is carried out with nitrogen according to corresponding volume method. (with sample preparation about 3g+/-5% (heat 3.0 DEG C/min until target temperature 50 DEG C) of weighing: 10 hours/50 DEG C)
The demonstration of BET data, with respect to other composition by directly compression-type sweet mellow wine and disintegrant form, according to the present invention, product is characterised in that obviously higher BET surface area. The surface area of this increase is relevant to the very good compressibility of material of the present invention, and with the immediately disintegrable qualitative correlation of the consequent tablet that contains disintegrant.

Claims (18)

  1. In direct tablet compressing technique for the preparation of the blend of rapid disintegration tablet, its byThe spray-dired sweet mellow wine of 90-98 weight portion and the crosslinked sodium carboxymethylcellulose of 10-2 weight portionComposition, is characterized in that, described blend has at 1.9-4.0m2BET table within the scope of/gArea.
  2. According to claim 1 in direct tablet compressing technique for the preparation of rapid disintegration tabletBlend, it is by the spray-dired sweet mellow wine of 95 weight portion and the crosslinked carboxymethyl of 5 weight portionsSodium cellulosate composition, is characterized in that, described blend has 1.9-4.0m2The BET table of/gArea.
  3. 3. according to the blend of claim 1, it is characterized in that, described blend has1.9-2.6m2BET surface area within the scope of/g.
  4. 4. according to the blend of claim 1-3 any one, it is characterized in that, bulk density is0.45-0.60g/ml, compacted density is 0.60-0.75g/ml, mobile inclination angle is 30-38 °.
  5. 5. according to the blend of claim 1-3 any one, it is characterized in that, average grain diameter existsWithin the scope of 60-200 μ m.
  6. 6. according to the blend of claim 5, it is characterized in that, average grain diameter is at 64-114 μ mIn scope.
  7. 7. according to the blend of claim 1-3 any one, the water of its have < 1 % by weight containsAmount.
  8. 8. according to the blend of claim 1-3 any one, it is characterized in that, it is compressibleOne-tenth tablet, and obtain and there is hardness > 250N, friability after the pressure lower compression of 20kNThe tablet of degree≤0.14% and disintegration time≤70 second.
  9. 9. contain active component and/or the tablet formulation agent containing spices, want by using according to rightAsk the blend of 1-8 any one to prepare as carrier material.
  10. 10. the purposes as carrier material according to the blend of claim 1-8 any one, instituteState carrier material for the preparation of containing vitamin, mineral matter, trace element, functional food ingredientsTablet formulation agent.
  11. 11. according to the blend of claim 1-8 any one as the purposes of carrier material, instituteState carrier material for the preparation of the tablet formulation agent containing plant component.
  12. 12. according to the purposes of claim 11, it is characterized in that, described plant component is plantExtract.
  13. 13. according to the blend of claim 1-8 any one as the purposes of carrier material, instituteState carrier material for the preparation of tablet formulation agent, this tablet formulation agent contains synthetic with naturalDyestuff; Natural with give the material of taste with natural consistent spices and other.
  14. 14. according to the purposes of claim 13, described spices and other material choosing of giving tasteSweetener from following: Aspartame, asccharin, acesulfam-K K, neohesperidin DC, trichlorine halfLactosucrose; Thaumatin and stevioside, or fruit flavors, mint flavouring, menthol; Be selected from lemonLemon acid and tartaric tartaric acid, or give the plant extracts of taste.
  15. 15. according to the blend of claim 1-8 any one as the purposes of carrier material, instituteState carrier material for the preparation of tablet formulation agent, this tablet formulation agent contains and has pharmacotoxicological effectMaterial.
  16. 16. according to the purposes of claim 15, described in there is pharmacotoxicological effect material be antiacidAgent, anti-infective, antalgesic, antiallergic, antiemetic and antidiarrheal agent.
  17. 17. according to the purposes of claim 15, described in there is pharmacotoxicological effect material be forAt the material of oral cavity and throat's local action.
  18. 18. according to the purposes of claim 16, and wherein said antalgesic is opioid.
CN200980127245.8A 2008-06-20 2009-05-25 Tablet matrix that can directly compress and quickly disintegrated Active CN102088959B (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP08011238.6 2008-06-20
EP08011238 2008-06-20
EP08014287 2008-08-11
EP08014287.0 2008-08-11
PCT/EP2009/003677 WO2009152922A1 (en) 2008-06-20 2009-05-25 Directly injection moldable and rapidly disintegrating tablet matrix

Publications (2)

Publication Number Publication Date
CN102088959A CN102088959A (en) 2011-06-08
CN102088959B true CN102088959B (en) 2016-05-25

Family

ID=41134695

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200980127245.8A Active CN102088959B (en) 2008-06-20 2009-05-25 Tablet matrix that can directly compress and quickly disintegrated

Country Status (15)

Country Link
US (1) US11166917B2 (en)
EP (1) EP2299982B1 (en)
JP (1) JP5756749B2 (en)
KR (1) KR101647855B1 (en)
CN (1) CN102088959B (en)
AR (1) AR072259A1 (en)
BR (1) BRPI0914164B1 (en)
CA (1) CA2728436C (en)
CL (1) CL2009001450A1 (en)
CO (1) CO6321152A2 (en)
ES (1) ES2676288T3 (en)
MX (1) MX2010014209A (en)
RU (1) RU2519768C2 (en)
TR (1) TR201808694T4 (en)
WO (1) WO2009152922A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112012027303A2 (en) * 2010-04-27 2017-10-24 Bayer Ip Gmbh oral crumbling tablet containing acarbose
EP2455069A1 (en) * 2010-11-11 2012-05-23 Laburnum GMBH Non-active administration form, method for producing same and use of same
ES2784134T3 (en) * 2012-04-27 2020-09-22 Merck Patent Gmbh Coated tablets and production thereof
CN105517576A (en) * 2013-07-06 2016-04-20 株式会社大赛璐 Ultrafast-disintegrating tablet and method for manufacturing same
FR3132522A1 (en) * 2022-02-08 2023-08-11 Roquette Freres Directly compressible mannitol granules
WO2023151868A1 (en) * 2022-02-08 2023-08-17 Roquette Freres Directly compressible mannitol granules

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4439858A1 (en) * 1994-11-08 1996-05-09 Merck Patent Gmbh By co-spray drying available polyol composition
CN1494419A (en) * 2001-03-06 2004-05-05 协和发酵工业株式会社 Preparations quickly disintegrating in oral cavity

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US100419A (en) * 1870-03-01 Improved rudder-collar
JPH08208523A (en) * 1995-02-03 1996-08-13 Gun Ei Chem Ind Co Ltd Material for pharmaceutical preparation
JP2001114712A (en) * 1996-04-16 2001-04-24 Takeda Chem Ind Ltd D-mannitol and method for producing the same
DE19615418A1 (en) 1996-04-22 1997-10-23 Merck Patent Gmbh Polyol composition
DE19617487A1 (en) 1996-05-02 1997-11-06 Merck Patent Gmbh Taste improvement of active pharmaceutical ingredients
JP3195290B2 (en) 1997-03-31 2001-08-06 キヤノン株式会社 Image forming device
US20020071864A1 (en) * 1999-03-25 2002-06-13 Yuhan Corporation Rapidly disintegrable tablet for oral administration
DE19927537A1 (en) 1999-06-16 2000-12-21 Merck Patent Gmbh Spray drying plant and method of using it
JP3435664B2 (en) * 1999-12-08 2003-08-11 ヤンセンファーマ株式会社 Oral fast disintegrating tablet and method for producing the same
US6316029B1 (en) 2000-05-18 2001-11-13 Flak Pharma International, Ltd. Rapidly disintegrating solid oral dosage form
CA2424770A1 (en) * 2000-10-06 2003-04-03 Takeda Chemical Industries, Ltd. Solid pharmaceutical preparation
DE10161402A1 (en) 2001-12-13 2003-06-18 Merck Patent Gmbh Process for the production of directly tablettable beta-mannitol
US7118765B2 (en) * 2001-12-17 2006-10-10 Spi Pharma, Inc. Co-processed carbohydrate system as a quick-dissolve matrix for solid dosage forms
ES2199061B1 (en) 2002-06-10 2005-02-16 Laboratorios Vita, S.A. TROUBLE-BASED TABLETS AND PROCEDURE FOR OBTAINING.
AU2004212976A1 (en) * 2003-02-19 2004-09-02 Biovail Laboratories Inc. Rapid absorption selective 5-HT agonist formulations
DE602004017847D1 (en) * 2003-04-08 2009-01-02 Novartis Ag SOLID PHARMACEUTICAL PHARMACEUTICAL FORMS USING A S1P RECEPTOR AGONIST AND A SUGAR ALCOHOL
US7282217B1 (en) * 2003-08-29 2007-10-16 Kv Pharmaceutical Company Rapidly disintegrable tablets
JP2005306770A (en) 2004-04-21 2005-11-04 Toa Eiyo Ltd Intraoral quick collapse type preparation and method for producing the same
JP5208348B2 (en) 2004-05-13 2013-06-12 旭化成ファーマ株式会社 Medicine containing naphthopidyl
GB0423800D0 (en) * 2004-10-27 2004-12-01 Orexo Ab New pharmaceutical formulations
IS7748A (en) 2005-03-17 2006-09-18 Actavis Group Composition for tablets containing topiramate
JP2008534562A (en) * 2005-03-28 2008-08-28 オレクソ・アクチエボラゲット New pharmaceutical compositions useful for the treatment of migraine
WO2007029376A1 (en) 2005-09-02 2007-03-15 Fuji Chemical Industry Co., Ltd. Orally rapidly disintegrating tablet
WO2007043538A1 (en) * 2005-10-05 2007-04-19 Kyoto Pharmaceutical Industries, Ltd. Composition for oral administration
GB0523810D0 (en) * 2005-11-23 2006-01-04 Astrazeneca Ab Pharmaceutical compositions
US20090186081A1 (en) 2006-01-05 2009-07-23 Lifecycle Pharma A/S Disintegrating Loadable Tablets
US20100004279A1 (en) * 2006-12-07 2010-01-07 Tomoyuki Watanabe Solid medicinal preparation containing mannitol or lactose
CA2687794C (en) * 2007-05-28 2015-01-27 Jin Satomi Spherical particle of crystalline mannitol

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4439858A1 (en) * 1994-11-08 1996-05-09 Merck Patent Gmbh By co-spray drying available polyol composition
CN1494419A (en) * 2001-03-06 2004-05-05 协和发酵工业株式会社 Preparations quickly disintegrating in oral cavity

Also Published As

Publication number Publication date
BRPI0914164B1 (en) 2019-04-30
CN102088959A (en) 2011-06-08
CO6321152A2 (en) 2011-09-20
RU2011130597A (en) 2013-01-27
JP5756749B2 (en) 2015-07-29
CA2728436C (en) 2016-07-26
AR072259A1 (en) 2010-08-18
US20110091545A1 (en) 2011-04-21
US11166917B2 (en) 2021-11-09
WO2009152922A1 (en) 2009-12-23
TR201808694T4 (en) 2018-07-23
MX2010014209A (en) 2011-02-21
JP2011524386A (en) 2011-09-01
EP2299982B1 (en) 2018-04-04
BRPI0914164A2 (en) 2015-10-20
RU2519768C2 (en) 2014-06-20
CA2728436A1 (en) 2009-12-23
CL2009001450A1 (en) 2010-06-11
KR20110022061A (en) 2011-03-04
KR101647855B1 (en) 2016-08-11
EP2299982A1 (en) 2011-03-30
ES2676288T3 (en) 2018-07-18

Similar Documents

Publication Publication Date Title
CN102088959B (en) Tablet matrix that can directly compress and quickly disintegrated
ES2745438T3 (en) Robust formulation of fast disintegrating tablets
TWI583387B (en) Fast disintegrating solid dosage form formulation comprising functionalized calcium carbonate and method of their manufacture
EP2334202B1 (en) Tabletting of ervthritol
CN113966174A (en) Pouch product with liquid flavor composition
SK286951B6 (en) Granules consisting of starch and lactose and method for the preparation thereof
JP4532903B2 (en) Fine particle composition
EP2467029A1 (en) Tabletting of erythritol and isomalt
US20170189338A1 (en) Tableting agent having a low water content, and method for the production thereof
US20130072578A1 (en) Orodispersible tablets of erythritol and isomalt
ES2720626T3 (en) Compressible polyol combination directly
CN114727952A (en) Stable effervescent co-processing excipient composition and preparation method thereof
JP2000264835A (en) Tablet composition containing sugar alcohol
JP2018150242A (en) Cellulose composite

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant